Traumatic brain injury (TBI) in older adults is common, accounting for over 25% of brain injuries in the US each year, with considerable mortality, long-term impairment and disability. Outcomes among older adults with TBI are disparately worse when compared to their younger counterparts with similar injuries. Clinical efforts to treat TBI in older adults have not yielded the expected improvements in physical impairment, disability and health- related quality of life. A critical barrier to the management of TBI is that there is limited knowledge about potential differences in the response to TBI that results from aging, and how older age may affect pathology and recovery following TBI. The current application proposes to use a novel set of immune biomarkers to enhance knowledge of the trajectory of recovery from TBI and the underlying mechanisms responsible for chronic symptoms, impairment and decrements in health-related quality of life in older adults following TBI. We propose that aging is a biological factor that contributes to the pathological response to injury by modulating the immune response to TBI and will test this hypothesis using a novel model of impairment and disability. The aims of this prospective cohort study are to: 1) Compare cellular immune responses, plasma inflammatory biomarker concentrations, and measures of impairments, disability and health-related quality of life up to 6 months post-injury in young and older adults with and without mild TBI (75 per group) and 2) Determine the association between selected cellular immune and plasma biomarkers and impairments, disability and health- related quality of life at 3 and 6 months post-injury in older adults with mild TBI. PUBLIC HEALTH RELEVANCE: Traumatic brain injury (TBI) in the elderly is a major and important clinical public health issue, accounting for more than 25% of TBIs the US each year. Functional and quality of life outcomes following TBI among older adults are poorer compared to younger counterparts with similar injuries and efforts to treat TBI in older adults have not yielde expected improvements in outcome. In this proposal we seek to explicate the biological rationale for this, and identify targets for possible treatment by testing the hypothesis that poorr outcomes are related to an altered immune response following TBI in the older adult.